There are may examples of persistant virus diseases in man which are disabling or fatal and resist treatment, yet the immunological and virological mechanisms are ill understood. The study of the murine-lymphocytic choriomenigitis virus (LCMV) system has thus far contributed a major share of what is known about viral immunopathology, including concepts of tolerance, immune complex disease, and lymphocyte killing. Therefore, immunological and virological factors contributing to the meaintenance of chronic virus infections will be examined, using predominately the murine-LCMV system. The role of defective interfering (DI) virus in limiting cell destruction, spread of infection, and antigenic expression in the mouse will be studied. The macrophage will be studied in respect to its ability to clear virus infectivity and virus infected cells from animals and cell culture. The nature of the cell killing ability of activated macrophages and of natural killer cells will be analyzed in acute and chronic LCMV infections in the mouse. In particular the target antigens for natural killer cells will be assessed, as well as the role of natural killer cells in clearing virus infected targets in vivo.